MODE OF ACTION STUDY OF NSP01-E, A POTENTIAL TREATMENT FOR ALZHEIMER’S DISEASE, IN PROTECTION AGAINST AMYLOID B PEPTIDE (AB) INJURY

Abstract

We studied an Asiatic plant traditionally used since decades as tonic and a wellbeing medicine. Thanks to our GREEN extraction platform (Greenform©) we realized and standardized a simplified plant exact (SPE) called NSP01-E well analytically characterized. This standardized specific SPE was tested on primary cell-based pharmacological models of neurodegenerative diseases. In this study, we used an in vitro model of AβO injuries (on primary cortical neurons) and we decided to carefully dissect the mode of action of NSP01-E. Using several antagonists acting on TrK/MEK, Pi3K/AKT, iNOS, PPARγ pathways and apoptosis pathway. For analysing the activation of different pathway, we observed the level of protein with an automatically western blot. We observed a strong neuro-protective and restorative effect against the Aβ induced injuries on cortical primary neurons, a well described Alzheimer’s disease (AD) models. We observed that NSP01-E partly acted though RAS/RAF, and inducible iNOS pathway. Additionally, the PPARγ survival pathway seemed to be activated. But more interestingly, AKT pathway and anti-apoptosis effector BCl2 were essential to its neuroprotective effect. Western blot analyses were also performed and confirmed the activation of these pro-survival pathways (ERK1/2) as well as the reduction of mitochondrial stress effectors (Cytochrome C…). These findings demonstrate that NSP01-E counters Aβ-dependent neuronal cell death and may represent a therapeutic intervention to limit neuronal death in Alzheimer disease.